Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 311, Issue 1, Pages E269-E277Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00524.2015
Keywords
early growth response factor 1; gene expression; inflammation; obesity; reproduction
Categories
Funding
- US Department of Agriculture-Agricultural Research Service Project [6026-51000-010-05S]
- ARS [813598, ARS-0426492] Funding Source: Federal RePORTER
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Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n = 7) compared with lean (LN; n = 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P < 0.001), greater fat mass (P < 0.001), and reduced lean mass (P < 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 ( P < 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (+/- 1.3 fold, P < 0.05). RT-qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNF alpha in ovaries from OB compared with LN (P < 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P < 0.05), whereas nuclear levels of Egr-1 (P < 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P < 0.05) correlated with % visceral fat weight (r = 0.51, -0.77, and -0.57, respectively, P <= 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels.
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